Jianwen Jin1, Yichao Zhao1, Sara Helen Kyne1, Kaveh Farshadfar2, Alireza Ariafard3,4, Philip Wai Hong Chan5,6. 1. School of Chemistry, Monash University, Clayton, Victoria, Australia. 2. Department of Chemistry, Islamic Azad University, Poonak, Tehran, Iran. 3. Department of Chemistry, Islamic Azad University, Poonak, Tehran, Iran. alireza.ariafard@utas.edu.au. 4. School of Natural Sciences-Chemistry, University of Tasmania, Hobart, Tasmania, Australia. alireza.ariafard@utas.edu.au. 5. School of Chemistry, Monash University, Clayton, Victoria, Australia. phil.chan@monash.edu. 6. Department of Chemistry, University of Warwick, Coventry, UK. phil.chan@monash.edu.
Abstract
Strategies that enable intermolecular site-selective C-H bond functionalisation of organic molecules provide one of the cornerstones of modern chemical synthesis. In chloroalkane synthesis, such methods for intermolecular site-selective aliphatic C-H bond chlorination have, however, remained conspicuously rare. Here, we present a copper(I)-catalysed synthetic method for the efficient site-selective C(sp3)-H bond chlorination of ketones, (E)-enones and alkylbenzenes by dichloramine-T at room temperature. A key feature of the broad substrate scope is tolerance to unsaturation, which would normally pose an immense challenge in chemoselective aliphatic C-H bond functionalisation. By unlocking dichloramine-T's potential as a chlorine radical atom source, the product site-selectivities achieved are among the most selective in alkane functionalisation and should find widespread utility in chemical synthesis. This is exemplified by the late-stage site-selective modification of a number of natural products and bioactive compounds, and gram-scale preparation and formal synthesis of two drug molecules.
Strategies that enable intermolecular site-selective C-H bond functionalisation of organic molen class="Chemical">cules provide one of the cornerstones of modern chemical synthesis. In chloroalkane synthesis, such methods for intermolecular site-selective aliphatic C-H bond chlorination have, however, remained conspicuously rare. Here, we present a copper(I)-catalysed synthetic method for the efficient site-selective C(sp3)-H bond chlorination of ketones, (E)-enones and alkylbenzenes by dichloramine-T at room temperature. A key feature of the broad substrate scope is tolerance to unsaturation, which would normally pose an immense challenge in chemoselective aliphatic C-H bond functionalisation. By unlocking dichloramine-T's potential as a chlorine radical atom source, the product site-selectivities achieved are among the most selective in alkane functionalisation and should find widespread utility in chemical synthesis. This is exemplified by the late-stage site-selective modification of a number of natural products and bioactive compounds, and gram-scale preparation and formal synthesis of two drug molecules.
Authors: Marcelo Zaldini Hernandes; Suellen Melo T Cavalcanti; Diogo Rodrigo M Moreira; Walter Filgueira de Azevedo Junior; Ana Cristina Lima Leite Journal: Curr Drug Targets Date: 2010-03 Impact factor: 3.465